Open Label Extension Study To Investigate Long Term Safety, Tolerability And Efficacy Of Pf-02545920 In Subjects With Huntington's Disease Who Completed Study A8241021

An Open Label Extension Study To Investigate The Long Term Safety, Tolerability And Efficacy Of Pf-02545920 In Subjects With Huntington's Disease Who Previously Completed Study A8241021

This study is a 12 month open label extension study of PF-02545920 20 mg dosed BID following study A8241021 in subjects with HD. Primary endpoints will be to assess long-term safety and tolerability of 20 mg BID of PF-02545920. Secondary endpoints will be the change from baseline in the Total Motor Score (TMS)assessment, and/ior the Total maximum Chorea (TMC) assessment of the Unified Huntington Disease Rating Scale (UHDRS) after 6 and 12 months of treatment, and Clinical Global Impression-Improvement score after 6 and 12 months of treatment. Subjects, who were assigned to the 20 mg PF-02545920 dose group in the preceding A8241021 study, will receive 20 mg PF-02545920 without any titration. All other subjects will be titrated to the 20 mg BID dose as follows: 5 mg BID for 7 days, 10 mg BID for 7 days, 15 mg BID for 7 days, then 20 mg BID for the remainder of the treatment phase. Up to 260 subjects may take part in this open label extension

Study Overview

• Status: Terminated
• Conditions: Huntington's Disease
• Intervention / Treatment: Drug: 20 mg BID of PF-02545920

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • The Centre For Huntington Disease, The University of British Columbia
  • Ontario
    • Toronto, Ontario, Canada, M3B 2S7
      • Center For Movement Disorders
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM-Notre-Dame Hospital
    • Montreal, Quebec, Canada, H4L 4M1
      • CHUM-Notre-Dame, Pharmacie
• Germany
  • Aachen, Germany, 52074
    • Uniklinik RWTH Aachen
  • Berlin, Germany, 10117
    • Charite - Universitatsmedizin Berlin
  • Bochum, Germany, 44791
    • St. Josef Hospital
  • Erlangen, Germany, 91054
    • Friedrich-Alexander-Universität
  • Lübeck, Germany, 23562
    • Universität zu Lübeck
  • Marburg, Germany, 35043
    • Philipps Universität Marburg
  • Munchen, Germany, 81675
    • Technische Universität München
  • Münster, Germany, 48149
    • George-Huntington-Institut
  • Taufkirchen, Germany, 84416
    • Kbo-Isar-Amper-Klinikum gGmbH
  • Ulm, Germany, 89081
    • Universitatsklinikum Ulm
  • Wuerzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
• Poland
  • Gdansk, Poland, 80462
    • Copernicus Podmiot Leczniczy sp.zo.o
  • Krakow, Poland, 31505
    • Krakowska Akademia Neurologii Sp. zo.o
  • Poznan, Poland, 60-529
    • SOLUMED Centrum Medyczne
  • Warszawa, Poland, 02957
    • Instytut Psychiatrii i Neurologii, I Klinika Neurologiczna
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZA
    • NHS Grampian, Aberdeen Royal Infirmary, Clinical Genetics Centre
  • Cardiff, United Kingdom, CF14 4XW
    • Institute of Psychological Medicine and Clinical Neurosciences
  • Glasgow, United Kingdom, G51 4TF
    • NHS Greater Glasgow and Clyde
  • London, United Kingdom, WC1N 3BG
    • University College London Hospitals Nhs Foundation Trust
  • London, United Kingdom, SE19RT
    • Guy's and St. Thomas' NHS Foundation Trust
  • London, United Kingdom, wc1b 5eh
    • University College London Hospitals Huntington's Diesease
  • Manchester, United Kingdom, M13 9WL
    • The National Institute for Health Research / Wellcome Trust Clinical Research Facility
  • Newcastle upon Tyne, United Kingdom, NE4 5PL
    • Newcastle Magnetic Resonance Centre
  • Oxford, United Kingdom, OX3 9DU
    • Oxford University Hospitals NHS Trust
  • Sheffield, United Kingdom, S10 2JF
    • Sheffield Teaching Hospital NHS Foundation Trust
  • Southampton, United Kingdom, SO16 6YD
    • University Hospital Southampton NHS Foundation Trust, Wessex Neurological Centre
  • Manchester
    • Oxford Road, Manchester, United Kingdom, M13 9WL
      • Central Manchester University Hospitals NHS Foundation Trust
  • Newcastle UPON TYNE
    • Gosforth, Newcastle UPON TYNE, United Kingdom, NE3 3XT
      • St Nicholas Hospital
  • WEST Midlands
    • Birmingham, WEST Midlands, United Kingdom, B15 2FG
      • Bimingham & Solihull Mental Health NHS Foundation Trust Department of Neuropsychiatry
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35233
      • The Kirkland Clinic of UAB Hospital
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • Los Angeles, California, United States, 90095
      • UCLA Radiology
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center Drug Information Center
    • Los Angeles, California, United States, 90095
      • UCLA Neurology Clinic
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center
  • Florida
    • Gainesville, Florida, United States, 32607
      • University of Florida Center for Movement Disorders & Neurorestoration
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Neuroscience Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43221
      • The Ohio State University
    • Columbus, Ohio, United States, 43221
      • The Wexner Medical Center at the Ohio State University
    • Columbus, Ohio, United States, 43221
      • The Wright Center of Innovation- The Ohio State University
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must have completed study A8241021
• Diagnosis of HD, including ≥36 CAG repeats.

Exclusion Criteria:

• Significant neurological disorder other than Huntington's disease.
• WBC ≤ 3500/mm3 AND/OR ANC ≤ 2000/mm3 and history of neutropenia or myeolo-proliferative disorders.
• Any drug related SAE experienced during study A8241021 which were not approved as acceptable for enrollment in A8241022.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 20 mg BID PF-02545920 non-titrated; Subjects who received 20 mg BID in completed study A8241021 will continue to receive 20 mg BID PF-02545920	Drug: 20 mg BID of PF-02545920; All subject who completed A8241021 will receive 20 mg BID (with or without titration)
Experimental: 20mg BID PF-02545920 titrated; Subjects who received either Placebo or 5mg BID of PF-02545920 in completed study A8241021 will be titrated up to 20 mg with 5mg increment per week, over 4 weeks (5mg increment/wk)	Drug: 20 mg BID of PF-02545920; All subject who completed A8241021 will receive 20 mg BID (with or without titration)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of its causal relationship with study treatment. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; was life-threatening (immediate risk of death); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs are events between first dose of study treatment and up to 28 calendar days after the last administration of study treatment that were absent before treatment or that worsened after treatment. AEs included both serious and non-serious AEs.	1 year
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, eosinophils, monocytes, basophils, and lymphocytes), chemistry (blood urea nitrogen/urea, creatinine, glucose, glycosylated hemoglobin [diabetics only], calcium, phosphorus, magnesium, creatine kinase, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein), urinalysis (color, appearance, specific gravity, pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, and microscopy), and other tests (follicle stimulating hormone, urine drug screen, urine pregnancy [human chorionic gonadotropin, hCG], serum beta hCG). Abnormality was determined by the investigator.	1 year
Number of Participants With Vital Signs Data Meeting Categorical Summarization Criteria	Number of participants with vital signs data meeting the following criteria is presented: (1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); (2) standing SBP <90 mmHg; (3) supine diastolic blood pressure (DBP) <50 mmHg; (4) standing DBP <50 mmHg; (5) supine pulse rate <40 beats per minute (bpm); (6) supine pulse rate >120 bpm; (7) standing pulse rate <40 bpm; (8) standing pulse rate >140 bpm; (9) maximum increase from baseline in supine SBP >= 30 mmHg; (10) maximum increase from baseline in standing SBP >= 30 mmHg; (11) maximum increase from baseline in supine DBP >= 20 mmHg; (12) maximum increase from baseline in standing DBP >= 20 mmHg; (13) maximum decrease from baseline in supine SBP >=30 mmHg; (14) maximum decrease from baseline in standing SBP >=30 mmHg; (15) maximum decrease from baseline in supine DBP >=20 mmHg; (16) maximum decrease from baseline in standing DBP >=20 mmHg.	1 year
Number of Participants With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria	Maximum absolute values and increases from baseline were summarized for PR interval (interval between the start of the ECG P wave and the start of the QRS complex corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization), QRS complex (time from Q wave to the end of the S wave corresponding to ventricular depolarization), and QTcF interval (time from ECG Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula). Number of participants with ECG data meeting the following criteria is presented: (1) PR interval >=300 msec; (2) QRS complex >=140 msec; (3) QTcF interval: 450 to <480 msec; (4) QTcF interval: 480 to <500 msec; (5) QTcF interval >=500 msec; (6) PR interval increase from baseline >=25/50 percent; (7) QRS complex increase from baseline >=50 percent; (8) QTcF interval increase from baseline: 30 to <60 msec; (9) QTcF interval increase from baseline >=60 msec.	1 year
Number of Participants With Abnormal White Blood Cell Count and Absolute Neutrophil Count (Without Regard to Baseline Abnormality)	Number of participants with white blood cell (WBC) count and absolute neutrophil count (ANC) meeting the following criteria is presented: (1) WBC count <0.6 *the lower limit of normal (LLN); (2) WBC count >1.5 times the upper limit of normal (ULN); (3) ANC <0.8*LLN; and (4) ANC >1.2*ULN.	1 year
Number of Participants With Laboratory Test Abnormalities (Normal Baseline)	The laboratory test included: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, eosinophils, monocytes, basophils, and lymphocytes), chemistry (blood urea nitrogen/urea, creatinine, glucose, glycosylated hemoglobin [diabetics only], calcium, phosphorus, magnesium, creatine kinase, sodium, potassium, chloride, total carbon dioxide, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein), urinalysis (color, appearance, specific gravity, pH, qualitative glucose, qualitative protein, qualitative blood, ketones, nitrites, leukocyte esterase, and microscopy), and other tests (follicle stimulating hormone, urine drug screen, urine pregnancy [human chorionic gonadotropin, hCG], serum beta hCG). Abnormality was determined by the investigator.	1 year
Number of Participants With Adverse Events Related to Extrapyramidal Symptoms by Severity	Adverse events related to extrapyramidal symptoms included dystonia, akathisia, tardive dyskinesia). Severity was assessed by the investigator. Mild means the AE didn't interfere with the participant's usual function. Moderate means the AE interfered to some extent the participant's usual function. Severe means the AE interfered significantly with the participant's usual function.	1 year
Number of Participants in Each Columbia Classification Algorithm of Suicide Assessment (C-CASA) Category	Columbia Suicide Severity Rating Scale (C-SSRS) was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior, and was used in this study. C-SSRS responses were mapped onto the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Number of participants with any of the following behaviors occurring since last visit was summarized: completed suicide; suicide attempt; preparatory acts towards suicide; suicidal ideation; self-injurious behavior (no suicidal intent).	Baseline (Day 1), Weeks 2 and 4, Months 3, 6, 9 and 12, follow-up visit (7-14 days after the last dose of Month 12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score	The UHDRS is a clinical rating scale developed to provide a uniform assessment of the clinical features and course of Huntington's disease (HD). The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. Total Motor Score (TMS) assesses motor features of HD with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural ability. The total motor impairment scores was the sum of all the individual 31 motor sub-items (each rated from 0 to 4), with higher scores indicating more severe motor impairment than lower scores. The range of TMS is 0-124.	Baseline (Day 1), Month 6, and Month 12
Change From Baseline in Unified Huntington's Disease Rating Scale (UHDRS) Total Maximum Chorea (TMC) Score	The UHDRS is a clinical rating scale developed to provide a uniform assessment of the clinical features and course of Huntington's disease (HD). The components of the full UHDRS assess motor function, cognition, behavior and functional abilities. Total Maximum Chorea (TMC) is a subset of the TMS assessment, and composed of the scoring of 7 chorea assessments (face, orobuccolingual, trunk, right and left upper extremities, right and left lower extremities). Each assessment is rated from 0 to 4 (absent to prolonged). TMC is obtained by adding up each of the separate scores, leading to max score of 28. The minimum score is 0. The higher the score, the worse the symptoms.	Baseline (Day 1), Month 6, and Month 12
Absolute Value in Clinical Global Impression of Improvement (CGI-I) Score	The Clinical Global Impression of Improvement (CGI-I) is a global measure of improvement or change based on the clinician's assessment of all available clinical data obtained from interviewing the participant. The CGI-I consists of a single 7-point rating of total improvement or change from baseline severity, regardless of whether or not the change is due entirely to drug treatment. Raters select 1 response based on the following question, "Compared to your participant's condition at the beginning of treatment, how much has he/she changed?" Scores are: 1: Very much improved; 2: Much improved; 3: Minimally improved; 4: No change; 5: Minimally worse; 6: Much worse; or 7: Very much worse.	Month 6 and Month 12

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2015
• Primary Completion (Actual): February 6, 2017
• Study Completion (Actual): February 6, 2017

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: January 15, 2015
• First Posted (Estimate): January 21, 2015

Study Record Updates

• Last Update Posted (Actual): April 23, 2018
• Last Update Submitted That Met QC Criteria: March 23, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Huntington; chorea; total motor score; CAG repeat: total functional capacity; motor cognitive and behavioral symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: A8241022; 2014-004900-31 (EudraCT Number); OPEN LABEL TO A8241021 (Other Identifier: Alias Study Number)